The major objective of this research is to determine how renal glycogen synthase is regulated and to apply any new insights gained to the regulation of glycogen synthase in other mammalian tissues. While much is known about the regulation of glycogen synthase in tissues with relatively high concentrations of glycogen, little is known about the regulation of glycogen synthase in tissues which contain relatively low concentrations of glycogen. Of particular interest is the kidney since there is a large difference in the synthesis of glycogen in the cortex and medulla even though glycogen levels are low in both portions of the kidney. The specific goals of this project are: 1) To purify and characterize renal glycogen synthase kinases and to establish the physiological significance and regulation of these enzymes in the medulla and cortex. Special emphasis will be placed on the role of cyclic AMP-independent glycogen synthase kinases as well as cyclic AMP-dependent protein kinase. 2) To purify and characterize renal glycogen synthase I and D and to establish how they are regulated in the cortex and medulla. 3) To purify and characterize renal glycogen synthase phosphatases and to establish their physiological significance and regulation in the cortex and medulla.